Elective Single Embryo Transfer: an update to UK Best Practice Guidelines

Figures & data

Table I. Summary of Global legislation in relation to eSET (adapted from Maheshwari et al., 2011).

Country	Legislation
Australia	No legislation; eSET advised < 35 on first fresh cycle. No more than 2 advised < 40
Austria	Legislation restricts the number of eggs which can be used in IVF. All fertilised embryos must be transferred
Belgium	Legislation; < 36 first cycle must have eSET
Canada	No overall legislation only guidelines suggesting eSET in patient < 35 years in a first or second cycle and consider eSET in patients 36 &37 with good prognosis. Quebec introduced legislation in 2010 which states every cycle should be eSET unless there are suboptimal conditions and clinical justification is given
Denmark	No legislation
Estonia	Max of 3 can be transferred
Finland	No legislation
France	Restricted to DET. If more than 2 clinical justification required
Germany	Legislation restricts the number of eggs which can be used in IVF. All fertilised embryos must be transferred
Greece	No legislation; recommended up to 3 embryos transferred for women up to age of 40 and up to 4 > 40.
Hungary	State regulation limits number to transfer to 3 except in exceptional circumstances when up to 4 can be transferred
India	Guidelines: Max of 3 can be transferred
Italy	Law restricts number of eggs which can be fertilised, all resulting embryos must be replaced
Japan	Recommendation by Japanese Society of Obs and Gynae; max 2 embryos since 2008
Luxemburg	No legislation
Netherlands	No legislation
New Zealand	Guidance related to funding. If publically funded < 35, first or second cycle eSET. No more than 2 embryos (fresh or frozen) < 40.
Norway	No legislation
Portugal	Law contains general addict that multiple embryos should be avoided if possible
Sweden	State legislation states in principle only 1 embryo should be replaced apart from in exceptional circumstances
Switzerland	Legislation restricts the number of eggs which can be used in IVF. All fertilised embryos must be transferred
Turkey	Legislation in March 2010 favouring eSET - limits < 35 to eSET and > 35 to DET.
USA	No overall legislation. Guidelines (ASRM, 2013a) suggest eSET should be offered to patients < 35 and no more than 2 embryos should be transferred. Patients 37–39 no more than 2 cleavage embryos in favourable prognosis patients or if blastocyst transfer. If using cleavage stage transfer in poor prognosis no more than 3 embryos should be replaced. No more than 3 embryos cleavage or 2 blastocysts in patients 38–40 years with favourable prognosis. Other patients in this group no more than 4 cleavage embryos or 3 blastocysts transferred. In patients 41–42 no more than 5 cleavage stage embryos or 3 blastocysts. In patients with 2 or more previous failed cycles one additional embryo can be transferred in each age category. No limit on patients over 43 years old In donor cycles if the donor is < 35 eSET should be strongly recommended

Key: eSET = elective single embryo transfer; DET = Double Embryo Transfer.

Table II. NICE hierarchy of evidence, and grading the strength of the evidence.

	Hierarchy of evidence
1a	Systematic review and meta-analysis of randomised controlled trials (RCTs)
1b	At least one randomised controlled trial
2a	At least one well-designed controlled study without randomisation
2b	At least one other type of well-designed quasi-experimental study
3	Well-designed non-experimental descriptive studies, such as comparative studies, correlation studies or case studies
4	Expert committee reports or opinions and/or clinical experience of respected authorities

	Grade strength of evidence
A	Requires at least one RCT as part of a body of literature of overall good quality and consistency addressing the specific recommendations. (Evidence levels 1a, 1b)
B	Requires the availability of well-controlled clinical studies but no randomised clinical trials on the topics of recommendation. (Evidence levels 2a, 2b, 3)
C	Requires evidence obtained from expert committee reports of opinions and/or clinical experiences of respected authorities. Indicates an absence of directly applicable clinical studies of good quality. (Evidence level 4)
GPP	Good practice point

Table III. NICE (2013) Guidelines – Embryo transfer strategy summary table (including fresh & frozen embryos).

Attempt	< 37		37–39		40–42
First Cycle	SET		> 1 Top Quality Available SET	No Top Quality Available Consider DET	Consider DET
Second Cycle	> 1 Top Quality Available SET	No Top Quality Available Consider DET	> 1 Top Quality Available SET	No Top Quality Available Consider DET	*
Third Cycle	No more than 2 embryos		No more than 2 embryos		*

Key: *NICE only recommend a single treatment cycle in women > 40 years of age; SET = Single Embryo Transfer; DET = Double Embryo Transfer.

Table IV. Timing of observation of fertilised oocytes and embryos and expected stage of development at each time point (ALPHA, 2011).

Type of Observation	Timing (hours PI)	Expected Stage of Development
Fertilisation Check	17 ± 1	Pronuclear Stage
Syngamy Check	23 ± 1	50 % in syngamy (up to 20 % at 2-cell stage)
Early Cleavage Check	26 ± 1 post ICSI 28 ± 1 post IVF	2-cell stage
Day 2 Embryo Assessment	44 ± 1	4-cell stage
Day 3 Embryo Assessment	68 ± 1	8-cell stage
Day 4 Embryo Assessment	92 ± 2	Morula
Day 5 Embryo Assessment	116 ± 2	Blastocyst

Key: PI = Post Insemination

Figure 1. Comparison of Clinical Pregnancy Rate (CPR), Multiple Pregnancy Rate (MPR) and Multiple Birth Rate (MBR) in women of all ages, fresh and frozen transfers combined (most recent HFEA data, personal communication). Note: MPR data for 2014 and MBR data for 2013 are based upon mid-year figures (HFEA, 2015).

Maheshwari, A., Griffiths, S., & Bhattacharya, S. (2011). Global variation in the uptake of single embryo transfer. Human Reproduction Update, 17, 107–120.

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ASRM. (2013a). Practice Committee of American Society for Reproductive Medicine; Practice Committee of Society for Assisted Reproductive Technology. Criteria for number of embryos to transfer: a committee opinion. Fertility & Sterility, 99, 44–46.

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National Institute for Health and Care Excellence. (2013). Fertility: assessment and treatment for people with Fertility problems. Clinical Guidelines CG156, http://www.nice.org.uk/guidance/cg156. Last accessed 13th May 2015.

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Alpha Scientists in Reproductive Medicine, ESHRE Special Interest Group in Embryology. (2011). Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Reproductive BioMedicine Online, 22, 632–646.

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HFEA. (2015). Improving outcomes for fertility patients: Multiple Births 2015. Available online at http://www.hfea.gov.uk/docs/Multiple_Births_Report_2015.pdf. Last accessed 22nd July 2015.

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